Glutamate controls the induction of GABA-Mediated giant depolarizing potentials through AMPA receptors in neonatal rat hippocampal slices

Glutamate controls the induction of GABA-Mediated giant depolarizing potentials through AMPA receptors in neonatal rat hippocampal slices
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DOI:
10.1152/jn.1999.81.5.2095
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发表时间:
1999-05-01
影响因子:
2.5
通讯作者:
Cherubini, E
Cherubini, E
中科院分区:
医学3区
文献类型:
--
作者:
Bolea, S;Avignone, E;Cherubini, E

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Giant depolarizing potentials (GDPs) are generated by the interplay of the depolarizing action of GABA and glutamate. In this study, single and dual whole cell recordings tin current-clamp configuration were performed from CA3 pyramidal cells in hippocampal slices obtained from postnatal (P) days P1- to pg-old rats to evaluate the role of ionotropic glutamate receptors in GDP generation. Superfusion of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10-40 mu M) completely blocked GDPs. However, in the presence of CNQX, it was still possible to re-induce the appearance of GDPs with GABA (20 I-LM) or (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxadepropionate(AMPA) (5 mu M). This effect was prevented by the more potent and selective AMPA receptor antagonist GYKI 53655 (50-100 mu M). In the presence of GYKI 53655, both kainic or domoic acid (0.1-1 mu M) were unable to induce GDPs. In contrast, bath application of D-(-)-2-amino-5-phosphonopentanoicacid (50 mu M)or (+)-3-(2-carboxy-piperazin-4-yl)-propyl-L-phosphonic acid (20 mu M) Produced only a 37 +/- 9% (SE) and 36 +/- 11% reduction in GDPs frequency, respectively. Cyclothiazide, a selective blocker of AMPA receptor desensitization, increased GDP frequency by 76 +/-: 14%. Experiments were also performed with an intracellular solution containing KF to block GABA, receptor-mediated responses. In these conditions, a,glutamatergic component of GDP was revealed. GDPs could still be recorded synchronous with those detected simultaneously with KCl-filled electrodes, although their amplitude was smaller. Similar results were found in pair recordings obtained from minislices containing only a small portion of the CA3 area. These data suggest that GDP generation requires activation of AMPA receptors by local release of glutamate from recurrent collaterals.